ABSTRACT
Nitric oxide (NO) is a small radical species involved in several fundamental physiological processes, including the control of vascular tone, the immune response and neuronal signalling. Endothelial dysfunction with the decreased NO bioavailability is the underlying cause of several diseases and has led to the development of a wide range of systemic NO donor compounds to lower the blood pressure and control hypertensive crises. However, several potential therapeutic actions of NO, not related to the cardiovascular system, demand exclusively local actions. Primary S-nitrosothiols (RSNOs) are endogenously found NO carriers and donors and have emerged as platforms for the localized delivery of NO in topical applications. Formulations for this purpose have evolved from low molecular weight RSNOs incorporated in polymeric films, hydrogels and viscous vehicles, to polymeric RSNOs where the SNO moiety is covalently bound to the polymer backbone. The biological actions displayed by these formulations include the increase in dermal vasodilation, the acceleration of wound healing, the killing of infectious microorganisms and an analgesic action against inflammatory pain. This MiniReview focuses on the state of the art of experimental topical formulations for NO delivery based on S-nitrosothiols and their potential therapeutic applications.
Subject(s)
Analgesics, Short-Acting/administration & dosage , Drug Delivery Systems , Nitric Oxide/administration & dosage , S-Nitrosothiols/chemistry , Vasodilator Agents/administration & dosage , Administration, Topical , Analgesics, Short-Acting/chemistry , Analgesics, Short-Acting/therapeutic use , Animals , Drug Delivery Systems/trends , Drug Liberation , Drug Stability , Humans , Hydrogels/chemistry , Molecular Weight , Nitric Oxide/chemistry , Nitric Oxide/therapeutic use , Photochemical Processes , Vasodilator Agents/chemistry , Vasodilator Agents/therapeutic use , Wound Healing/drug effectsABSTRACT
OBJECTIVE: To study the relationship between the use of psychotropic and opioid medications with workers' compensation disability and costs. METHODS: The study population included lost time claimants injured between 1999 and 2002 followed to closing in December 31, 2009. RESULTS: Controlling for age, sex, marital status, attorney involvement, and spinal surgeries, multivariate logistic regression revealed that odds ratios (95% confidence interval) of claim costs ≥$100,000 compared with claimants who were never prescribed opioids were 4.3 for short-acting opioids only; 8.6 for any use of long-acting opioids; 2.8 for any use of hypnotics; 2.6 for any use of antipsychotics; 1.6 for any use of anti-anxiety agents; and 2.9 for any use of antidepressants. CONCLUSIONS: The use of psychotropic and opioid medications was associated with high workers' compensation costs and prolonged disability.
Subject(s)
Analgesics, Opioid , Drug Prescriptions/statistics & numerical data , Occupational Injuries/economics , Psychotropic Drugs , Sick Leave/statistics & numerical data , Workers' Compensation/economics , Analgesics, Opioid/economics , Analgesics, Opioid/therapeutic use , Analgesics, Short-Acting/economics , Analgesics, Short-Acting/therapeutic use , Anti-Anxiety Agents/economics , Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/economics , Antidepressive Agents/therapeutic use , Antipsychotic Agents/economics , Antipsychotic Agents/therapeutic use , Humans , Hypnotics and Sedatives/economics , Hypnotics and Sedatives/therapeutic use , Psychotropic Drugs/economics , Psychotropic Drugs/therapeutic useABSTRACT
In clinical trials a single dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has shown a rapid antidepressant effect in patients with treatment-resistant depression and bipolar depression. The implications of glutaminergic mechanisms in depression and the rapid effect of a single dose of ketamine could open new pathways to understand the pathophysiology of depression and the development of novel rapid-acting antidepressant drugs.
